Figure 2.

Schematic of the pathobiological features of d16HER2. The homodimerization of the d16HER2 splice isoform results in autophosphorylation of the tyrosine kinase domains and induction of downstream signaling. Cell signaling downstream of d16HER2 is transduced to the nucleus through different circuitries including Mitogen-Activated Protein Kinase (MAPK), Protein Kinase B (AKT), and mainly by Proto-oncogene tyrosine-protein kinase Src (SRC). Through the activation of these downstream pathways, d16HER2 is able to increase tumorigenicity and sensitivity to anti-HER2 drugs and enhance tumor aggressiveness and metastatization. d16HER2 also induces activation of the epithelial–mesenchymal transition (EMT) program and the enrichment of cancer stem cells (CSCs) inside the tumor. Created by Biorender.com.